dbSNP rs3176767: ICAM3:c.77-127A>C (chr19-10339075-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001320606.2(ICAM3):c.-282A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 998,410 control chromosomes in the GnomAD database, including 22,640 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3229 hom., cov: 32)

Exomes 𝑓: 0.21 ( 19411 hom. )

Consequence

ICAM3
NM_001320606.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.64

Publications

25 publications found

Variant links:

Genes affected

ICAM3 (HGNC:5346): (intercellular adhesion molecule 3) The protein encoded by this gene is a member of the intercellular adhesion molecule (ICAM) family. All ICAM proteins are type I transmembrane glycoproteins, contain 2-9 immunoglobulin-like C2-type domains, and bind to the leukocyte adhesion LFA-1 protein. This protein is constitutively and abundantly expressed by all leucocytes and may be the most important ligand for LFA-1 in the initiation of the immune response. It functions not only as an adhesion molecule, but also as a potent signalling molecule. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2016]

ICAM3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047955513).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320606.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ICAM3	NM_002162.5	MANE Select	c.77-127A>C	intron	N/A	NP_002153.2	P32942
ICAM3	NM_001320606.2		c.-282A>C	5_prime_UTR	Exon 2 of 7	NP_001307535.1
ICAM3	NM_001320605.2		c.77-127A>C	intron	N/A	NP_001307534.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ICAM3	ENST00000160262.10	TSL:1 MANE Select	c.77-127A>C	intron	N/A	ENSP00000160262.3	P32942
ICAM3	ENST00000589261.5	TSL:1	n.252A>C	non_coding_transcript_exon	Exon 2 of 7
ICAM3	ENST00000912542.1		c.77-127A>C	intron	N/A	ENSP00000582601.1

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30752

AN:

151734

Hom.:

3231

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.298

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.246

Gnomad EAS

AF:

0.120

Gnomad SAS

AF:

0.257

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.231

Gnomad OTH

AF:

0.225

GnomAD2 exomes

AF:

0.192

AC:

19986

AN:

104130

AF XY:

0.194

show subpopulations

Gnomad AFR exome

AF:

0.147

Gnomad AMR exome

AF:

0.185

Gnomad ASJ exome

AF:

0.243

Gnomad EAS exome

AF:

0.112

Gnomad FIN exome

AF:

0.165

Gnomad NFE exome

AF:

0.204

Gnomad OTH exome

AF:

0.207

GnomAD4 exome

AF:

0.209

AC:

177266

AN:

846558

Hom.:

19411

Cov.:

AF XY:

0.212

AC XY:

91468

AN XY:

430894

show subpopulations

African (AFR)

AF:

0.150

AC:

3040

AN:

20262

American (AMR)

AF:

0.175

AC:

4559

AN:

26006

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

4097

AN:

17020

East Asian (EAS)

AF:

0.130

AC:

4526

AN:

34744

South Asian (SAS)

AF:

0.266

AC:

15422

AN:

57908

European-Finnish (FIN)

AF:

0.202

AC:

6682

AN:

33098

Middle Eastern (MID)

AF:

0.243

AC:

786

AN:

3230

European-Non Finnish (NFE)

AF:

0.212

AC:

130024

AN:

614696

Other (OTH)

AF:

0.205

AC:

8130

AN:

39594

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

7320

14641

21961

29282

36602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3374

6748

10122

13496

16870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.202

AC:

30746

AN:

151852

Hom.:

3229

Cov.:

AF XY:

0.201

AC XY:

14949

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.160

AC:

6646

AN:

41416

American (AMR)

AF:

0.179

AC:

2729

AN:

15212

Ashkenazi Jewish (ASJ)

AF:

0.246

AC:

854

AN:

3468

East Asian (EAS)

AF:

0.119

AC:

615

AN:

5174

South Asian (SAS)

AF:

0.256

AC:

1234

AN:

4816

European-Finnish (FIN)

AF:

0.207

AC:

2183

AN:

10536

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.231

AC:

15683

AN:

67918

Other (OTH)

AF:

0.222

AC:

468

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1286

2572

3857

5143

6429

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

348

696

1044

1392

1740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.222

Hom.:

10247

Bravo

AF:

0.198

TwinsUK

AF:

0.217

AC:

805

ALSPAC

AF:

0.236

AC:

908

ExAC

AF:

0.144

AC:

16334

Asia WGS

AF:

0.191

AC:

664

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.073

(source)

DANN

Benign

0.27

DEOGEN2

Benign

0.026

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.16

MetaRNN

Benign

0.0048

PhyloP100

-2.6

GERP RS

-6.2

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over